This project culminates a series of studies of transfusion-associated hepatitis (TAH) in prospectively followed transfusion recipients undergoing open-heart surgery. The studies have sequentially shown the efficacy of adopting an all volunteer donor system, testing for the hepatitis B surface antigen, utilizing the surrogate assays, alanine aminotransferase (ALT) and anti-hepatitis B core antibody (anti-HBc), and testing for antibodies to the hepatitis C virus (HCV). Overall, the studies have shown a decline in TAH incidence from near 30 percent in the 1960s, 10 to 20 percent in the 1970s, 8 to 12 percent in the early 80s, and 4 to 5 percent in the late 80s. Since 1990, the study has focused on the impact of the introduction of donor screening assays to detect carriers of (HCV). Following first generation anti-HCV testing, introduced in 1990, the rate of TAH fell from 3 to 4 percent to 1.5 percent. Since the introduction of more sensitive second generation assays in 1992, we have followed over 650 recipients and the overall TAH rate has fallen to 0.2 percent while the rate of transfusion associated hepatitis C has fallen to zero. The overall rate reflects only a single mild case whose etiology is undetermined. Hence, in this approximate 30-year span, we have documented the virtual disappearance of TAH.A new prospective study is being initiated that will follow both adult and pediatric patients for a large variety of potential transfusion-transmitted infections. We will continue to look for HBV, HCV, HIV, and HTLV infections to monitor the continued efficacy of existing donor screening measures. However, the main thrust of the study will be to determine the incidence and clinical outcome of infections for which donor screening is not routinely performed. This would include newly proposed hepatitis viruses (TTV and SEN-V), cytomegalovirus (CMV), parvovirus B-19, and the human herpes virus, type 8 (HHV-8). Other infections such as borrelia (lyme disease), babesia (babesiosis), trypanosoma cruzi (Chagas) and HHV-6 may also be monitored. Although, we will continue to measure serologic responses, the study will focus on molecular assays. A primary goal of the study will be to establish a linked donor and recipient repository that can be used to rapidly assess if a newly emergent agent represents a threat to the blood supply. This repository will be linked to the RADAR repository.